Page last updated: 2024-10-24

ISGF3 complex

Definition

Target type: cellularcomponent

A transcription factor complex that consists of a Stat1-Stat2 heterodimer and the IRF9 protein. [GOC:mah, PMID:8943351]

The ISGF3 complex, also known as the interferon-stimulated gene factor 3 complex, is a multi-subunit transcription factor that plays a crucial role in mediating the cellular response to interferons (IFNs). It is formed upon activation by IFNs and comprises four main protein components:

1. **STAT1 (Signal Transducer and Activator of Transcription 1):** STAT1 is a latent transcription factor that, upon IFN stimulation, becomes phosphorylated by Janus kinases (JAKs). Phosphorylated STAT1 then dimerizes with another phosphorylated STAT1 molecule, forming a STAT1 homodimer.

2. **STAT2 (Signal Transducer and Activator of Transcription 2):** Similar to STAT1, STAT2 is also a latent transcription factor that is phosphorylated by JAKs upon IFN stimulation. The phosphorylated STAT2 then forms a heterodimer with STAT1, forming the STAT1:STAT2 heterodimer.

3. **IRF9 (Interferon Regulatory Factor 9):** IRF9, also known as ISGF3 gamma, is a DNA-binding transcription factor that interacts with the STAT1:STAT2 heterodimer. The interaction of IRF9 with the STAT1:STAT2 heterodimer creates the complete ISGF3 complex.

4. **p48 (48 kDa Protein):** p48, also known as ISGF3 epsilon, is a protein that acts as a chaperone for the ISGF3 complex. It facilitates the assembly and nuclear translocation of the complex.

The cellular component of the ISGF3 complex is primarily located in the **nucleus** of the cell. Upon IFN stimulation, the complex translocates from the cytoplasm to the nucleus, where it binds to specific DNA sequences called **interferon-stimulated response elements (ISREs)**. Binding to ISREs triggers the transcription of genes involved in the antiviral response, including genes encoding antiviral proteins, immune modulators, and cell cycle regulators. In addition to its role in the antiviral response, ISGF3 also plays a role in regulating cell growth, differentiation, and apoptosis.'
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Proteins (1)

ProteinDefinitionTaxonomy
Signal transducer and activator of transcription 1-alpha/betaA signal transducer and activator of transcription 1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P42224]Homo sapiens (human)

Compounds (6)

CompoundDefinitionClassesRoles
suramin sodiumsuramin sodium : An organic sodium salt that is the hexasodium salt of suramin. It is an FDA approved drug for African sleeping sickness and river blindness.organic sodium saltangiogenesis inhibitor;
antinematodal drug;
antineoplastic agent;
apoptosis inhibitor;
EC 2.7.11.13 (protein kinase C) inhibitor;
GABA antagonist;
GABA-gated chloride channel antagonist;
purinergic receptor P2 antagonist;
ryanodine receptor agonist;
trypanocidal drug
epigallocatechin gallate(-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin.

epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis)
flavans;
gallate ester;
polyphenol
antineoplastic agent;
antioxidant;
apoptosis inducer;
geroprotector;
Hsp90 inhibitor;
neuroprotective agent;
plant metabolite
nsc 74859NSC 74859: inhibits Stat3 binding activity; structure in first source

S3I-201 : An amidobenzoic acid obtained by formal condensation of the carboxy group of [(4-methylbenzene-1-sulfonyl)oxy]acetic acid with the amino group of 4-amino-2-hydroxybenzoic acid.
amidobenzoic acid;
monohydroxybenzoic acid;
tosylate ester
STAT3 inhibitor
nf 449
5,15-diphenylporphine5,15-diphenylporphine: structure in first source
guttiferone kguttiferone K: antiproliferative compound of Rheedia calcicola from the Madagascar rain forest; structure in first source